Taxotere is a drug used in combination with other therapies for the treatment of breast cancer, lung cancer, prostate cancer and stomach cancer as well as head/neck cancer. It is part of a family of drugs derived from the Pacific yew tree known as Taxanes and was catapulted to the headlines in the 1990s as a new treatment option with promising results, especially for sufferers of metastatic cancer. The promise of Taxotere however, comes with some substantial side effects due to its toxicity and dosage must be tightly controlled by prescribing physicians. Among the more controversial side effects, which is presently the subject of ongoing litigation, is the drug’s propensity for causing permanent hair loss (alopecia) in patients.
Prescription Name and Overview
Taxotere is the product name for the drug docetaxel. It is only available by prescription and is used in combination with other chemotherapy drugs as part of a larger cancer treatment strategy, particularly in patients suffering from metastasized forms of: breast, lung, prostate, stomach and head/neck cancer. Taxane works through a mechanism known as microtubule function disruption. Microtubules are central to the process of cell division in the human body and intereference with their function inhibits the division and spread of cancerous cells (“mitotic inhibition”). Originally approved for use by the Food and Drug Administration (FDA) in 1996, Taxotere and other taxanes have grabbed headlines for their success in treating the spread of tumors and increased surivial rates – particularly for patients suffering with breast cancer. Taxotere’s effectiveness comes with some sigificant side effects due to its toxicity – including the risk of permanent hair loss.
Generic Name and Overview
Therapeutic equivalents to Taxotere are marketed under the product name Docetaxel.
OTC Name and Overview
Manufacturer
Taxotere (Docetaxel)
Sanofi S.A.
Labeled Indications
- Breast cancer: Treatment of breast cancer (locally advanced/metastatic) after prior chemotherapy failure; adjuvant treatment (in combination with doxorubicin and cyclophosphamide) of operable node-positive breast cancer
- Gastric cancer: Treatment of advanced gastric adenocarcinoma, including gastroesophageal junction adenocarcinoma (in combination with cisplatin and fluorouracil) in patients who have not received prior chemotherapy for advanced disease
- Head and neck cancer: Treatment (induction) of locally advanced squamous cell head and neck cancer (in combination with cisplatin and fluorouracil)
- Non-small cell lung cancer: Treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of prior platinum-based chemotherapy; treatment of previously untreated unresectable locally advanced or metastatic NSCLC (in combination with cisplatin)
- Prostate cancer: Treatment of metastatic castration-resistant prostate cancer (in combination with prednisone)
Dosages
Taxotere is packaged in a standard dosage form of: 20 mg/mL (1 mL); 80 mg/4 mL (4 mL) [contains alcohol, usp, polysorbate 80]. It is then prescribed in dosages warranted by the FDA approved labeling under the supervision of a physician in a properly equipped facility.
Breast Cancer
For locally advanced or metastatic breast cancer after failure of prior chemotherapy, the recommended dose of TAXOTERE is 60 mg/m2 to 100 mg/m2 administered intravenously over 1 hour every 3 weeks.
For the adjuvant treatment of operable node-positive breast cancer, the recommended TAXOTERE dose is 75 mg/m2 administered 1 hour after doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 every 3 weeks for 6 courses. Prophylactic G-CSF may be used to mitigate the risk of hematological toxicities.
Non-small Cell Lung Cancer
For treatment after failure of prior platinum-based chemotherapy, Taxotere was evaluated as monotherapy, and the recommended dose is 75 mg/m2 administered intravenously over 1 hour every 3 weeks. A dose of 100 mg/m2 in patients previously treated with chemotherapy was associated with increased hematologic toxicity, infection, and treatment-related mortality in randomized controlled trials.
For chemotherapy-naive patients, Taxotere was evaluated in combination with cisplatin. The recommended dose of Taxotere is 75 mg/m2 administered intravenously over 1 hour immediately followed by cisplatin 75 mg/m2 over 30–60 minutes every 3 weeks.
Prostate Cancer
For metastatic castration-resistant prostate cancer, the recommended dose of Taxotere is 75 mg/m2 every 3 weeks as a 1 hour intravenous infusion. Prednisone 5 mg orally twice daily is administered continuously.
Gastric Adenocarcinoma
For gastric adenocarcinoma, the recommended dose of Taxotere is 75 mg/m2 as a 1 hour intravenous infusion, followed by cisplatin 75 mg/m2, as a 1 to 3 hour intravenous infusion (both on day 1 only), followed by fluorouracil 750 mg/m2 per day given as a 24-hour continuous intravenous infusion for 5 days, starting at the end of the cisplatin infusion. Treatment is repeated every three weeks. Patients must receive premedication with antiemetics and appropriate hydration for cisplatin administration.
Head and Neck Cancer
Patients must receive premedication with antiemetics, and appropriate hydration (prior to and after cisplatin administration). Prophylaxis for neutropenic infections should be administered. All patients treated on the Taxotere containing arms of the TAX323 and TAX324 studies received prophylactic antibiotics.
- Induction Chemotherapy Followed by Radiotherapy (TAX323)
For the induction treatment of locally advanced inoperable SCCHN, the recommended dose of Taxotere is 75 mg/m2 as a 1 hour intravenous infusion followed by cisplatin 75 mg/m2 intravenously over 1 hour, on day one, followed by fluorouracil as a continuous intravenous infusion at 750 mg/m2 per day for five days. This regimen is administered every 3 weeks for 4 cycles. Following chemotherapy, patients should receive radiotherapy.
- Induction Chemotherapy Followed by Chemoradiotherapy (TAX324)
For the induction treatment of patients with locally advanced (unresectable, low surgical cure, or organ preservation) SCCHN, the recommended dose of Taxotere is 75 mg/m2 as a 1 hour intravenous infusion on day 1, followed by cisplatin 100 mg/m2 administered as a 30-minute to 3 hour infusion, followed by fluorouracil 1000 mg/m2/day as a continuous infusion from day 1 to day 4. This regimen is administered every 3 weeks for 3 cycles. Following chemotherapy, patients should receive chemoradiotherapy.
What Is It Used For?
Taxotere is widely regarded as one of the most important chemotherapeutic drugs in the cancer fighting arsenal today. It belongs to a class of drugs known as plant alkaloids – specifically taxanes from the bark of the Pacific yew tree, which attack cancerous cells during their phases of division. Once cancerous cells lose their ability to divide, other chemotheraphy agents can work to shrink tumors and stop the spread of cancer to other parts of the body.
How Does it Work?
Taxotere works by disrupting the microtubular network in cells, which is essential for cell division and other normal cellular functions. It then interferes with the function of microtubules, resulting in inactive microtubule bundles, causing cancerous cells to die.
What are the Approved Uses?
Taxotere is approved to be used either alone or in conjuction with other drugs to treat:
- Breast Cancer
- Non-Small Cell Lung Cancer
- Prostate Cancer
- Squamous Cell Carcinoma of the Head and Neck
- Stomach Adenocarcinoma
- Gastroesophageal Junction Adenocarcinoma
Production Anecdotes / History
Taxotere is a member of the family of taxanes, anti-cancer medications novel for not just their effectiveness and mode of action, but also for their being derived from the bark of yew trees. The drug Taxotere traces its roots back to the 1960s, and an initiative which collected Pacific yew tree specimens as part of the U.S. National Cancer Institute products screening program. In the 1970s and 80s studies began in earnest which investigated Taxotere’s effectiveness in advanced breast and ovarian cancer, against which it demonstrated exceptional effectiveness.
Despite its transformative impact on treating some forms of cancer, Taxotere is nonetheless a potent cytotoxin and presents significant dosing challenges. Since its introduction, patients and treating phyisicans have noted that side effects from Taxotere can range from the more mundane to severe – including the possibility of permanent hair loss (alopecia).
Precautions
It is very important for patients taking Taxotere to remain under the close supervision of the physician coordinating their cancer treatement. They may be asked to give frequent blood and urine tests to check for unwanted side-effects of the medication.
Taking Taxotere while pregnant may cause harm to an unborn baby, or cause birth defects – even if the father is using the medication when the mother becomes pregnant. Female patients should use effective birth control during treatment with this medicine and for 6 months after the last dose. Male patients who have female partners should use effective birth control during treatment with this medicine and for 3 months after the last dose.
Taxotere can also suppress immune function in patients by lowering the number of white blood cells in the bloodstream, and thereby increase the chance for infection. Additionally, Taxotere can lower the number of platelets necessary for proper bloodclotting function. Patients are advised to engage in recommnded changes to behavior to reduce the risk or incidence of accidental infection or bleeding.
Long-Term Use Considerations
Two of the most common long-term side effects of Taxotere chemotherapy are sensory and motor peripheral neuropathy. Grade 3 and 4 neuropathy is only observed in less than 10% of patients receiving Taxotere therapy. Major clinical symptoms include numbness and tingling of the hands and feet, with loss of reflexes. The incidence of neuropathy is dependent upon the total dose of the drug administered. In the Phase III clinical trial of metastatic breast cancer patients treated with Taxotere, neuropathy of grade 2 or greater began at a dosage of 371 mg/m2.71 The mainstay of treatment includes prompt recognition of onset of symptoms with subsequent delay of therapy or dose reduction.
Drug Interactions
CYP3A4 is an important enzyme that is found mainly within the liver and intestines. Taxotere is a “CYP3A4 substrate” meaning that its presence in the body is ultimately metabolized with the assistance of CYP3A4. Patients taking Taxotere may experience adverse health issues if they are also taking medication known as “CYP3A4 inhibitors or inducers”. Common inhibitors include (but are not limited to):
- Clarithromycin
- Erythromycin
- Diltiazem
- Itraconazole
- Ketoconazole
- Ritonavir
- Verapamil
- Goldenseal
- Grapfruit
- St. John’s Wort
Long-Term Side Effects
Neuropathy
Some chemotherapy patients prescribed Taxotere as part of their larger regimen report experiencing neuropathy of the hands and feet. Specifically, this is described as a numbness or tingling and loss of reflex. Some cases of neuropathy go away following treatment while others continue to experience this condition for some time.
Permanent Hair Loss
Taxotere is also linked with considerable hair loss in some patients. While hair loss is not uncommon during the course of chemotherapy, patients can generally expect that their hair will grow back following treatment. However, patients (in particular female ones) who were prescribed Taxotere experienced near total and permanent hair loss as a consequence of taking the drug.
FDA Warnings (History Of)
Taxotere’s FDA approved label includes a “black-box” warning concerning toxic deaths, hepatoxicity, neutropenia, hypersensitivity reactions and fluid retention. Additionally, Taxotere contains warnings concerning the potential for severe allergic reactions as well as birth defects in pregnant women and adverse health risks to breastfeeding children.
Other Common Side Effects
- Allergic reactions
- Susceptibility to infection
- Fluid retention
- Hair loss
- Numbness in the fingers and toes
- Changes in sense of taste
- Nausea
- Cough or hoarseness
- Pain or tenderness
- Vomiting
- Weight gain
- Constipation
- Black stools
- Difficulty swallowing
- Blood in the urine
- Arrhythmia
- Fatigue
- Myalgia
- Arthralgia
- Mouth sores
- Trouble breathing
- Watery eyes
Lawsuits
Women who have suffered permanent hair loss due to their being prescribed Taxotere are now filing lawsuits in court alleging that the drug’s manufacturer, Sanofi AG, (and its subsidiary, Sanofi-Aventis U.S., LLC) either hid or failed to properly warn of the risk of hair loss. Furthermore, they allege that had they known of the propensity Taxotere’s causing permanent hair loss, they would have opted for treatment with a similar drug, Taxol, which is just as effective and does not cause permanent hair loss.
To date, more than 10,000 lawsuits have been filed by surivors of breast cancer treatment with Taxotere. These lawsuits claim, among other things, that Sanofi made false and misleading statements promoting Taxotere as superior to Taxol, engaged in illegal kickbacks to healthcare providers, and either withheld or downplayed increasing scientific evidence that Taxotere was responsible for near total and permanent hair loss in some patients.
Some of these lawsuits commenced trial in 2019 with more to come in 2020. All Taxotere hair loss cases filed in federal court have been consolidated into a multi-district litigation (MDL) process in New Orleans.
Sources Cited (10)
1. “Taxotere Side Effects” https://www.rxlist.com/taxotere-drug.htm#side_effects
2. Docetaxel https://reference.medscape.com/drug/taxotere-docetaxel-342192#5
3. “Pharmacokinetics, dynamics and toxicity of docetaxel: Why the Japanese dose differs from the Western dose” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4452149/
4. “Docetaxel (Taxotere): an overview of first-line monotherapy.” https://www.ncbi.nlm.nih.gov/pubmed/8604448
5. “Taxotere FDA Approved Label” https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/020449orig1s075.pdf
6. “How bark from the Pacific yew tree improved the treatment of breast cancer” https://www.pharmaceutical-journal.com/news-and-analysis/news/how-bark-from-the-pacific-yew-tree-improved-the-treatment-of-breast-cancer/11084729.article?firstPass=false
7. “Persistent major alopecia following adjuvant docetaxel for breast cancer: incidence, characteristics, and prevention with scalp cooling” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6133184/
8. “Chemocare: Taxotere” http://chemocare.com/chemotherapy/drug-info/Taxotere.aspx
9. “OncoLink: Taxotere” https://www.oncolink.org/cancer-treatment/oncolink-rx/docetaxel-taxotere
10. “National Cancer Institute: Docetaxel” https://www.cancer.gov/about-cancer/treatment/drugs/docetaxel
Tracy Everhart
Tracy Everhart is the Editor for Drug Law Journal. A highly-trained and certified medical professional, Tracy is also an accomplished medical writer. After spending years on the front lines of the medical profession, Tracy now devotes her expertise and skills to researching and reporting on new drugs and devices that enter the market, as well as their side-effects and the real-life stories involved. Prior to joining Drug Law Journal, Tracy wrote for benchmark online healthcare resources focused on families and, in particular, women’s health issues. Tracy holds post-graduate degrees from both the American College of Healthcare Sciences and the Yale School of Nursing. She is also a graduate of both Hampshire College, where she studied microbiology and the University of South Carolina school of nursing.
